Eliminating Delirium and Brain Inflammation after Surgery

New study shows that electrical stimulation of the vagus nerve can reduce the inflammation and improve cognitive outcomes of patients after surgery.

by Kayt Sukel

November 26, 2018

Electrical stimulation of the brain could help reduce delirium, brain inflammation and long-lasting cognitive issues that many people, especially older adults, experience after surgery.

Researchers believe cognitive problems are caused by the body’s immune response to surgery, causing unwanted inflammation in the brain. A new study by researchers at Duke University shows that minimally invasive electrical stimulation of the vagus nerve, a cranial nerve that connects the brain to the body, can reduce the inflammation and improve cognitive outcomes. The study, conducted on rats, is the first step toward proving raises the stimulation technique could work in humans.

The vagus nerve is a complex entity. It is the longest of the 10 cranial nerves, with fibers that run from the brain all the way down to the abdomen. Given its anatomical reach, scientists have long hypothesized—and now scientifically demonstrated—that the vagus nerve plays a critical role in monitoring the body’s state by actively communicating with its most important organs, including the heart, lungs, and gut.

But its role in immune system regulation made Niccolò Terrando, Ph.D., an associate professor of anesthesiology at Duke University, wonder if this vital nerve could be harnessed to help reduce inflammation after surgical insult.

“We wanted to ameliorate the inflammatory response that we see in older adults after surgery,” he explained. “This response can lead to delirium and cognitive impairment in some patients and, long term, sometimes even dementia. We thought that if we can modulate the activation in the vagus nerve prior to or during surgery, we can regulate the immune response and stop this dangerous brain inflammation that can occur.”

Vagus stimulation is not new. There are surgically implanted stimulators to help manage epileptic symptoms, as well as non-invasive devices for treatment of chronic headaches that patients can use in their homes. But Terrando and his colleague Warren M. Grill, Ph.D., a biomedical engineer at Duke, wanted to create a more precise, minimally invasive stimulation device that could be used in surgical environments.

The team had no intention of implanting an entire stimulator. Instead, it used an ultrasound-guided needle to stimulate an area close to the cervical vagus nerve in mice.

“One of the principle challenges we had was making sure we were actually stimulating the vagus nerve and not something else,” Grill said. “We developed an imaging approach using Doppler ultrasound so we could see the nerve and then position a needle stimulating electrode just adjacent to it.”

The scientists then took measures of heart rate—a reduction in heart rate is a biomarker of vagus nerve stimulation—to ensure they were stimulating the vagus and not something else.

When the researchers tested the needle on mice for the relatively short time of 30 minutes, they found it reduced brain inflammation and improved cognitive outcomes after treatment. The results of this proof of concept study surprised Terrando.

“It is remarkable to me that by electrically stimulating this nerve we can improve brain-related outcomes,” he said. “This is one of the first descriptions that we can use nerve stimulation to regulate the body’s immune response.”

The researchers hope to follow this study with the development of a more refined and portable device that can survive the rigors of the operating room. They are now creating a wireless set-up, perhaps the needle stimulator fixed with a bandage that would be minimally invasive yet powerful enough to provide adequate stimulation and stable during surgical procedures.

“Moving forward, we need to think about how this might work in an operating room environment where you have patients being moved around, where patients may need to be intubated, and, of course, the anesthesiologist is going to want to monitor the patient,” he said. “How do we stabilize, physically, this needle electrode so we can deliver consistent stimulation of the vagus nerve no matter what’s happening with the patient?”

That will require some careful engineering, Grill said. For now, he’s pleased his team could demonstrate that such a short period of vagus nerve stimulation could have profound effects on the body’s response to inflammatory insult.

“This shows me that there is the possibility of using this kind of device as a preoperative prophylactic that can be delivered to a patient prior to surgery and that can subsequently impact the outcome of that surgery,” he said. “It’s pretty exciting.”